Somatic Mutation Theory - Why it's Wrong for Most Cancers

Abstract

Hysteron proteron reverses both temporal and logical order and this syllogism occurs in carcinogenesis and the somatic mutation theory (SMT): the first (somatic mutation) occurs only after the second (onset of cancer) and, therefore, observed somatic mutations in most cancers appear well after the early cues of carcinogenesis are in place. It is no accident that mutations are increasingly being questioned as the causal event in the origin of the vast majority of cancers as clinical data show little support for this theory when compared against the metrics of patient outcomes. Ever since the discovery of the double helical structure of DNA, virtually all chronic diseases came to be viewed as causally linked to one degree or another to mutations, even though we now know that genes are not simply blueprints, but rather an assemblage of alphabets that can, under non-genetic influences, be used to assemble a business letter or a work of Shakespearean literature. A minority of all cancers is indeed caused by mutations but the SMT has been applied to all cancers, and even to chemical carcinogenesis, in the absence of hard evidence of causality. Herein, we review the 100 year story of SMT and aspects that show why genes are not just blueprints, how radiation and mutation are associated in a more nuanced view, the proposed risk of cancer and bad luck, and the in vitro and in vivo evidence for a new cancer paradigm. This paradigm is scientifically applicable for the majority of non-heritable cancers and consists of a six-step sequence for the origin of cancer. This new cancer paradigm proclaims that somatic mutations are epiphenomena or later events occurring after carcinogenesis is already underway. This serves not just as a plausible alternative to SMT and explains the origin of the majority of cancers, but also provides opportunities for early interventions and prevention of the onset of cancer as a disease.

Science belongs to no one—and to everyone

“…The dogma that emerged and has persisted for 100 years is the theory that somatic mutation causes the majority of cancers [62]. Among the many possible reasons for the error are incomplete literature researches, receptive reading, or even a purposeful Ignoratio arbitraria.…”

“…Often, observations that are correctly expressed in a manuscript or scientific work are misinterpreted by readers who do not understand the science or the paper; things get lost in translation. How scientists generate data and statements that are later incorrectly interpreted has been described in a recent paper [62]. To wit, "… scientists searched for DNA mutations in 800 cancer patients (some 200 different cancer types) and compared the tumor DNA with the DNA of healthy cells of the same patients [69].…”

Pragmatic cancer approach − time to change?

“…First, the fashion was on "oncogenes" [5]. This, after a long delay, was displaced by tumor-suppressor genes.…”

“…This, after a long delay, was displaced by tumor-suppressor genes. The mentioned trends of cancer fashion was followed by others such as cell cycle gene mutation, apoptosis, aneuploidy, angiogenesis [4] and lastly "bad luck" [5][6][7].…”

“…Complexity of the data is the first problem of the project. Other problems are the lack of common mutations among tumors and cancer cells are often quick to become resistant, typically by activating different genes to bypass driver mutations that are blocked by targeted treatment [5]. Recently it was pointed out that cancer profiling may underestimate that two cancer cell clones may look identical yet differ completely at the protein level [10] In summary, this project has not succeeded in winning the fight against cancer, despite the high amount of resources spent [11,12].…”